The H-current is a very slow, depolarizing current that is hyperpolarization-activated (weird, right?)
Decreases Background Excitation ():
This hyperpolarizes the system to mimic a loss of brainstem input
Increases inhibition:
Increases max synaptic conductance ()
Increases decay time constant ()
Original hypothesis
Cartoon of mechanism compared to data
Our model network
Sustained Alpha
Sustained alpha NOT natural
Detail: is critical
induces sustained alpha
Detail: Propofol alpha mechanism
Sustained alpha summary
potentiation is the critical factor for sustained alpha!
Sustained alpha does NOT occur normally
potentiation uses spindling machinery (like ) to create sustained alpha
Note that we have ONLY simulated an isolated thalamus so far
Alpha-SWO Coupling
Recall: SWO
Recall: Our model network
Trough-max
Peak-max
Transition example
Alpha-SWO Coupling summary
Overall thalamic hyperpolarization is the critical factor for switching between trough-max and peak-max!
potentiation is required for any coupling, but cannot transform between PAC regimes!
Given SWO UP/DOWN transitions coming from cortex to thalamus,
trough-max alpha CAN be generated during DOWNs by the thalamus independently!
peak-max alpha CAN be generated during DOWNs by the thalamus independently as well, or in combination with corticothalamic spikes
Overall Modeling Conclusions
potentiation is the critical factor for sustained alpha, implying a thalamic component of propofol PAC
Once there is sustained alpha, thalamic hyperpolarization is the critical factor for switching between trough-max and peak-max, implying a brainstem component of propofol PAC
You need both to get switching between peak-max and trough-max in thalamocortical output
Overall Modeling Conclusions
Thus, our initial model was ONLY insufficient in that there are other constraints; you also need: